Linalool has two enantiomers, (R)-linalool and (S)-linalool. Both are known to possess several biological activities in stressed animals. Our previous work revealed that inhalation of (R)-linalool altered hypothalamic gene expression in rats under stress. In the present study, we monitored hypothalamic gene expression in restrained rats with and without (S)-linalool inhalation by DNA microarray. The entire gene expression profile showed that inhalation of (S)-linalool significantly changed the expression levels of 316 hypothalamic genes in the restrained rats. The differentially expressed genes (e.g., App, Avp, Igf2, Igfbp2, Sst and Syt5) were found to relate to cell-to-cell signaling and nervous system development. These results indicate that (S)-linalool influences hypothalamic gene expression in restrained rats, and that inhalation of (S)-linalool under the stressed condition has some effects on stress-related biological responses.